162229-14-3

Upstream product

• 98-03-3 thiophene-2-carbaldehyde 
• 105-45-3 acetoacetic acid methyl ester 
• 14205-39-1 methyl 3-aminocrotonate 
• 39562-41-9 (2-Thienylmethylen)acetessigsaeure-methylester 

Downstream Products

• 219701-24-3 dimethyl 2,6-dimethyl-4-(thiophen-2-yl)pyridine-3,5-dicarboxylate 

Relevant academic research and scientific papers

Thiophene substituted dihydropyridines

The crystal structures of 4-(2-thiophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-bis(methoxycarbonyl) (I)[a = 10.273(5) A, b = 10.428(5) A, c = 14.799(9) A, β = 98.13(4)°, P21/c], 4-(3-thiophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-bis(methoxycarbonyl) (II)[a = 10.636 (9) A, b = 10.372(8) A, c = 15.043(15) A, β = 98.13(6)°, P21/c], and 4-(2-thiophenyl)-2,6-dimethyl-l,4-dihydropyridine-3,5-bis(ethoxycarbonyl) (III) [a = 26.793(16) A, b = 7.610(6) A, c = 17.612(10) A, β = 97.61(2)°, C2/c] reveal patterns of hydrogen bonding pertinent to behavior of these members of the 1,4-dihydropyridine family in receptor site docking. Carbonyl groups substituted at C3 and C5 are seen in ap conformation when hydrogen bonded. Sulphur atoms of the hetero rings do not participate in hydrogen bonding. In these structures the position of the herero atom is seen to be disordered over two equivalent sites. Thus, there is no demonstrated preference for conformation of the hetero ring.

A Simple and Efficient One-pot Synthesis of 1,4-dihydropyridines Using Nano-WO3-supported Sulfonic Acid as an Heterogeneous Catalyst under Solvent-free Conditions

Nano-tungsten trioxide-supported sulfonic acid (n-WSA) was found to be an effective heterogeneous catalyst for the one-pot reaction of aromatic aldehydes, β-dicarbonyl compounds and ammonium acetate to afford 1,4-dihydropyridine derivatives in good to excellent yields. The other main advantages of the present method are short reaction times, simple workup, ease in purification and environmentally benign methodology. The reaction conditions were optimized employing Response Surface Method technique (Central Composite Design (CCD)) which is economically considerable because of the minimum number of experiments required to evaluate the effects of multiple parameters on the response.

Ultrasound-mediated, uranyl nitrate hexahydrate-catalyzed synthesis of 1,4-dihydropyridines under mild conditions

Abstract Synthesis of 1,4-dihydropyridines by three-component condensation reaction of aldehyde, 1,3-dicarbonyl compounds, and ammonium acetate have been found to be efficiently catalyzed by uranyl nitrate hexahydrate [UO2(NO3)2 ·6H2O] at room temperature under ultrasound irradiation. This novel synthetic method offers the advantages of high yields, short reaction times, simplicity, and easy workup compared to the conventional methods reported in the literature.

Multicomponent diversity-oriented synthesis of symmetrical and unsymmetrical 1,4-dihydropyridines in recyclable glycine nitrate (GlyNO 3) ionic liquid: A mechanistic insight using Q-TOF, ESI-MS/MS

Multicomponent reactions are compelling strategies for generating a chemically diverse set of multifunctionalized heterocyclic motifs with high atom economy, rendering the transformations green. These strategies can further become more prolific if catalyst recyclability, compatibility and exploration of precise mechanistic pathways are considered. To this end, an inexpensive and recyclable glycine nitrate (GlyNO3) ionic liquid has been efficiently employed to obtain diversely substituted symmetrical and unsymmetrical 1,4-dihydropyridines with up to 93% yields via three and four components, respectively. The catalyst recyclability and compatibility to obtain both symmetrical and unsymmetrical 1,4 DHPs under identical reaction conditions are added benefits to its practical utility. Furthermore, progress of the reaction was monitored by Q-TOF, direct infusion electrospray ionization mass spectrometry (ESI-MS), and key cationic intermediates involved in the reaction have been further identified by a tandem MS experiment (Q-TOF, ESI-MS/MS), which served as the proof of concept to the mechanistic model. This is the first report which revealed that the Hantzsch reaction predominantly follows the diketone pathway among four competing reaction pathways. the Partner Organisations 2014.

Alginic acid: A highly efficient renewable and heterogeneous biopolymeric catalyst for one-pot synthesis of the Hantzsch 1,4-dihydropyridines

Alginic acid, a naturally occurring polysaccharide, in its granular form and without any post-modification was found to be an efficient, environmentally benign, easily recoverable and low-cost catalyst for the clean and rapid synthesis of 1,4-dihydropiridine derivatives (DHPs) just based on its polysaccharide architecture. The Hantzsch pseudo-four-component reaction of ethyl or methyl acetoacetate, ammonium acetate and different aldehydes is catalyzed by alginic acid efficiently under mild conditions to afford the desired products in high to quantitative yields and clean reaction profiles. Avoiding the use of any transition metal, the use of a one-pot and multi-component procedure for the synthesis of DHPs, the reusability of the catalyst and operational simplicity are important features of this methodology.

Magnetic Fe3O4 nanoparticles: Efficient and recoverable nanocatalyst for the synthesis of polyhydroquinolines and Hantzsch 1,4-dihydropyridines under solvent-free conditions

A green approach for efficient and rapid synthesis of biologically active substituted Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives using magnetic Fe3O4 nanoparticles (Fe3O 4 MNPs) as a recyclable catalyst under solvent-free conditions was reported. The catalyst was characterized by FT-IR, XRD, and TEM analysis. Compared to the classical reactions, this method consistently has the advantages of short reaction times, little catalyst loading, high yields, easy magnetic separation and reusability of the catalyst.

Synthesis of 4-thiophen-2′-yl-1,4-dihydropyridines as potentiators of the CFTR chloride channel

The gating of the CFTR chloride channel is altered by a group of mutations that cause cystic fibrosis. This gating defect may be corrected by small molecules called potentiators. Some 1,4-dihydropyridine (DHP) derivatives, bearing a thiophen-2-yl and a furanyl ring at the 4-position of the nucleus, were prepared and tested as CFTR potentiators. In particular, we evaluated the ability of novel DHPs to enhance the activity of the rescued ΔF508-CFTR as measured with a functional assay based on the halide-sensitive yellow fluorescent protein. Most DHPs showed an effect comparable to or better than that of the reference compound genistein. The potency was instead significantly improved, with some compounds, such as 3g, 3h, 3n, 4a, 4b, and 4d, having a half effective concentration in the submicromolar range. CoMFA analysis gave helpful suggestions to improve the activity of DHPs.

An efficient, metal-free, room temperature aromatization of Hantzsch-1,4-dihydropyridines with urea-hydrogen peroxide adduct, catalyzed by molecular iodine

A mild, highly efficient and metal-free synthetic method for aromatization of 1,4-dihydropyridines employing urea-hydrogen peroxide adduct as oxidant catalyzed by 20 mol % of molecular iodine was developed. The reaction was carried out in ethyl acetate at room temperature and the products were isolated in high to excellent yields. A plausible free-radical mechanism is proposed based on results obtained with derivatives having alkyl and aryl substituents in the 1,4-dihydropyridine ring.

Synthesis and activities of a thienyl dihydropyridine series on intracellular calcium in a rat pituitary cell line (GH3/B6)

The synthesis of a thienyl dihydropyridine series according to the Hantzsch method is described. The influence of these derivatives on intracellular calcium ([Ca2+](i)) in GH3 cells was evaluated in vitro using spectrofluorimetry with indol as Ca2+ fluorescent probe. We compared their effects on [Ca2+](i) and hormone release with those of nifedipine. The most active tested compounds on [Ca2+](i) were those methylated on the 3-position of the thienyl ring (activity was about 75% of nifedipine). Interestingly, the most efficient compounds on [Ca2+](i) were also the most efficient on hormone release.